ArticleClinical epigenetics2020
DNA methylation mediates the effect of cocaine use on HIV severity.
Article in Clinical epigenetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Gene expression differences in differentially methylated sites associated with HIV status and cocaine use.Clinical and translational medicine · 2025Article
- Causal relationships between gut microbiota, plasma metabolites, and HIV infection: insights from Mendelian randomization and mediation analysis.Virology journal · 2024Article
- Cis-meQTL for cocaine use-associated DNA methylation in an HIV-positive cohort show pleiotropic effects on multiple traits.BMC genomics · 2023Article
- The link between chronic cocaine use, B cell perturbations, and blunted immune recovery in HIV-infected individuals on suppressive ART.NeuroImmune pharmacology and therapeutics · 2023Article
- Investigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia.Human molecular genetics · 2022Article
- Ageing and older people who use illicit opioids, cocaine or methamphetamine: a scoping review and literature map.Addiction (Abingdon, England) · 2022Article
- HIV Tat and cocaine interactively alter genome-wide DNA methylation and gene expression and exacerbate learning and memory impairments.Cell reports · 2022Article
- HIV-1 Tat and cocaine coexposure impacts piRNAs to affect astrocyte energy metabolism.Epigenomics · 2022Article
- Epigenome-wide epidemiologic studies of human immunodeficiency virus infection, treatment, and disease progression.Clinical epigenetics · 2022Review
- High-Dimensional DNA Methylation Mediates the Effect of Smoking on Crohn's Disease.Frontiers in genetics · 2022Article
- Identification of methylation signatures and rules for predicting the severity of SARS-CoV-2 infection with machine learning methods.Frontiers in microbiology · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCocaine use accelerates human immunodeficiency virus (HIV) progression and worsens HIV outcomes. We assessed whether DNA methylation in blood mediates the association between cocaine use and HIV severity in a veteran population.
methodsWe analyzed 1435 HIV-positive participants from the Veterans Aging Cohort Study Biomarker Cohort (VACS-BC). HIV severity was measured by the Veteran Aging Cohort Study (VACS) index. We assessed the effect of cocaine use on VACS index and mortality among the HIV-positive participants. We selected candidate mediators that were associated with both persistent cocaine use and VACS index by epigenome-wide association (EWA) scans at a liberal p value cutoff of 0.001. Mediation analysis of the candidate CpG sites between cocaine's effect and the VACS index was conducted, and the joint mediation effect of multiple CpGs was estimated. A two-step epigenetic Mendelian randomization (MR) analysis was conducted as validation.
resultsMore frequent cocaine use was significantly associated with a higher VACS index (β = 1.00, p = 2.7E-04), and cocaine use increased the risk of 10-year mortality (hazard ratio = 1.10, p = 0.011) with adjustment for confounding factors. Fifteen candidate mediator CpGs were selected from the EWA scan. Twelve of these CpGs showed significant mediation effects, with each explaining 11.3-29.5% of the variation. The mediation effects for 3 of the 12 CpGs were validated by the two-step epigenetic MR analysis. The joint mediation effect of the 12 CpGs accounted for 47.2% of cocaine's effect on HIV severity. Genes harboring these 12 CpGs are involved in the antiviral response (IFIT3, IFITM1, NLRC5, PLSCR1, PARP9) and HIV progression (CX3CR1, MX1).
conclusionsWe identified 12 DNA methylation CpG sites that appear to play a mediation role in the association between cocaine use and HIV severity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.